At present, treatments of diabetes are symptomatic and rely on administration of insulin or hypoglycemic agents. However, a long-term control of blood sugar is difficult, not to mention complete cure of diabetes, and in case of longer period of the disease, more diversified complications are induced. Of such complications, a general disease state of diabetic peripheral neuropathy is bilaterally symmetrical and sensory nerve dominant polyneuropathy. In acute symptoms, excitement of nerves such as sensory abnormality, allodynia (to feel pain by light touch of body surface) and the like is observed, and in chronic symptoms, diminished sensation (limb numbness, cold sense etc.), pain and the like are observed. In addition, diabetic dysautonomia is mainly developed in diabetic patients having polyneuropathy, thus putting every organ under control of autonomic nerve at risk for abnormality, and abnormal bowel movement such as constipation and diarrhea, impotence, orthostatic hypotension, dyshidrosis, gastric emptying delay and the like are observed.
For diabetic neuropathy showing such diversified symptoms, epalrestat (manufactured by Ono Pharmaceutical Co., Ltd.), which is an aldose reductase inhibitor, has been approved and used only in Japan. However, various problems have been pointed out as regards efficacy and side effects of this drug [The Informed Prescriber, vol. 11, pages 122 and 125, December (1996)]. Moreover, mexiletine hydrochloride (manufactured by Nippon Boehringer Ingelheim Co., Ltd.), which has been used as a therapeutic drug for tachyarrhythmia (ventricular), has been additionally approved and used for efficacy and effect in improvement of subjective symptoms (spontaneous pain, numbness) of diabetic neuropathy. However, its spontaneous pain relieving rate is not more than 50%, as reported in the Phase III—controlled clinical trial—, and the drug is not entirely satisfactory as a therapeutic agent for diabetic neuropathy.
The main purpose in present day therapy of diabetes is to prevent the onset and progress of diabetic complications, and the development of a drug for diabetic complications, which shows a high therapeutic effect and a high safety, is desired.
Under the circumstances, in a connection between nucleic acid related compounds and neuropathy, it has been reported that triacetyluridine is effective for peripheral neuropathy (diminished sensation) induced by taxol, which is an anticancer agent [WO 00/11952].
However, peripheral neuropathy induced by taxol, which is an anticancer agent, and diabetic neuropathy are completely different diseases in causes of onset. In addition, the above international publication does not consider or even suggest whether or not triacetyluridine is effective for neuropathy derived from metabolic disturbance of carbohydrate, namely, diabetic neuropathy. Moreover, the above international publication exemplarily indicates CDP-choline, other than triacetyluridine, as an active ingredient. However, CDP-choline is merely shown as an example in the above international publication, without any specific data, much less a description or data relating to the effect of CDP-choline on diabetic neuropathy.